- CDB-2914 is a hormone that blocks progesterone, which is necessary for maintaining pregnancy. In women with fibroid tumors, CDB-2914 shrank the tumors. In many cases, menstrual periods stopped during treatment. Because CDB-2914 decreased or stopped menstrual bleeding in women with fibroids, it may be able to treat abnormal periods in women without fibroids.

Objectives:

- To see whether CDB-2914 can treat abnormal uterine bleeding in premenopausal women.

Eligibility:

- Premenopausal women who have abnormal uterine bleeding that is not caused by fibroids.

Design:

Participants will be screened with a physical exam and medical history. They will also have blood and urine tests. An ultrasound with fluid of the uterus will test for fibroids. Uterine cells will be collected for biopsy.

For the next three menstrual cycles, participants will take either CDB-2914 or a placebo. Treatment will be studied with blood tests and symptom diaries.

At the end of the treatment, participants have three options. They can have surgery at the Clinical Center or have another 3 months of CDB-2914. The third option is to stop treatment at the Clinical Center.

Surgery will be either uterine ablation or hysterectomy. Only women older than age 33 may have a hysterectomy. Blood and urine samples will be collected after surgery.

Both surgery and further treatment participants will have followup exams.

All participants will have a final followup exam 1 year after stopping treatment.

Abnormal uterine bleeding is the most common gynecologic complaint in reproductive aged women. Medical treatment of abnormal uterine bleeding has high failure rates and surgical management remains the primary, definitive therapy. Most women undergoing hysterectomy for abnormal bleeding failed a therapeutic trial of medical management. Consequently, development of an efficacious, new medical treatment for abnormal uterine bleeding is urgently needed. Many of these reproductive aged women also need contraception. Ulipristal acetate (UPA), a novel progesterone receptor modulator developed at the NIH, has promise as an effective medical treatment for abnormal uterine bleeding and as a contraceptive agent. In women with symptomatic fibroids, UPA significantly reduced fibroid size, stopped menstrual bleeding and led to an increase in red blood cell hemoglobin. It also inhibited release of an egg from the ovaries (ovulation) without reducing estrogen levels or causing hot flashes, making contraception a potential future use.

This study will evaluate UPA effects on estrogen production and ovulation, and will determine whether it reduces bleeding in women who have abnormal uterine bleeding as assessed by the Menorrhagia Impact Questionnaire (MIQ) and menstrual calendars. Women with an anatomic abnormality of the uterus are not eligible to participate. Participants will take UPA (10 mg daily by mouth) or a similar-appearing inactive pill (placebo) for approximately 90 days. Women will be randomly assigned to receive daily UPA 10 mg, or a daily placebo tablet, during the initial three-month period. The participants and the investigators will not be informed of the treatment group. To understand the effects of UPA on the uterus and its lining (endometrium), women will have studies before and at the end of UPA treatment, including ultrasound imaging of the uterus after injection of a small amount of sterile saline into the uterine cavity, and a biopsy of the endometrium to examine the tissue under the microscope. Before and while taking study agent, women will record daily bleeding and complete the MIQ monthly. During the treatment period, blood will be taken weekly to measure hormone levels (to evaluate ovulation blockage), and monthly to evaluate safety. At the end of the randomized study period, the research team will offer participants additional options of UPA or surgical therapy. Women may choose surgical therapy at the NIH or may elect other treatment options elsewhere.

Eligibility

Ages Eligible for Study:

25 Years to 50 Years

Genders Eligible for Study:

Both

Accepts Healthy Volunteers:

No

Criteria

INCLUSION CRITERIA:

Female gender - to evaluate effects in the target population for clinical trials

In good health. Chronic medication use is acceptable except for glucocorticoid use. Other chronic medication use may be acceptable at the discretion of the research team. Interval use of over-the counter drugs is acceptable but must be recorded.

Ovulatory women will be defined as those who have menstrual cycles of 24 35 days and a progesterone value > 3.0 pg/mL between 5 and 9 days after in-home documentation of an LH surge

Anovulatory women will be defined as those without an in-house LH surge in whom progesterone values 3 and 4 weeks after menses are < 3.0 ng/mL

Use of estrogen or progesterone-containing compounds, such as oral contraceptives and hormone replacement therapy, within 8 weeks of study entry, including transdermal, injectable, vaginal and oral preparations

Current use of agents known to induce hepatic P450 enzymes; use of imidazoles

Current use of GnRH analogs or other compounds that affect menstrual cyclicity

Use of herbal medication having estrogenic or antiestrogenic effects within the past 3 months

FSH > 20 IU/mL

Untreated cervical dysplasia

Need for interval use of narcotics

Abnormal adnexal/ovarian mass

Contradiction to anesthesia, for women planning surgery

Leiomyomata, polyps or other anatomic causes of vaginal bleeding

Previous participation in the study

Thrombocytopenia defined as platelets < 150,000

Patients with known abnormal breast pathology

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study.
To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01493791